Abstract
Background
The contact factor XII (FXII) activates upon contact with a variety of charged surfaces. Activated FXII (FXIIa) activates factor XI, which activates factor IX, resulting in thrombin generation, platelet activation, and fibrin formation. In both in vitro and in vivo rabbit models, components of medical devices, including extracorporeal oxygenators, are known to incite fibrin formation in a FXII‐dependent manner. Since FXII has no known role in hemostasis and its inhibition is therefore likely a safe antithrombotic approach, we investigated whether FXII inhibition also reduces accumulation of platelets in extracorporeal oxygenators.
Objectives
We aimed to determine the effect of FXII inhibition on platelet deposition in perfused extracorporeal membrane oxygenators in nonhuman primates.
Methods
A potent FXII neutralizing monoclonal antibody, 5C12, was administered intravenously to block contact activation in baboons. Extracorporeal membrane oxygenators were temporarily deployed into chronic arteriovenous access shunts. Radiolabeled platelet deposition in oxygenators was quantified in real time using gamma camera imaging. Biochemical assays were performed to characterize the method of action of 5C12.
Results
The anti‐FXII monoclonal antibody 5C12 recognized both the alpha and beta forms of human and baboon FXII by binding to the protease‐containing domain, and inhibited FXIIa activity. Administration of 5C12 to baboons reduced platelet deposition and fibrin formation in the extracorporeal membrane oxygenators, in both the presence and absence of systemic low‐dose unfractionated heparin. The antiplatelet dose of 5C12 did not cause measurable increases in template bleeding times in baboons.
Conclusions
FXII represents a possible therapeutic and safe target for reducing platelet deposition and fibrin formation during medical interventions including extracorporeal membrane oxygenation.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details







1 Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA; Aronora, Inc., Portland, OR, USA
2 Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA
3 Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA
4 Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR, USA
5 Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA; Aronora, Inc., Portland, OR, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR, USA